TitleGenome-wide analysis of gene expression regulated by the calcineurin/Crz1p signaling pathway in Saccharomyces cerevisiae.
Publication TypeJournal Article
Year of Publication2002
AuthorsYoshimoto, H, Saltsman, K, Gasch, AP, Li, HXia, Ogawa, N, Botstein, D, Brown, PO, Cyert, MS
JournalJ Biol Chem
Date Published2002 Aug 23
KeywordsBinding Sites, Calcineurin, Calcium, DNA Methylation, DNA-Binding Proteins, Gene Expression Regulation, Fungal, Oligonucleotide Array Sequence Analysis, Promoter Regions, Genetic, Response Elements, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sodium, Trans-Activators, Transcription Factors

In Saccharomyces cerevisiae, the Ca(2+)/calmodulin-dependent protein phosphatase, calcineurin, is activated by specific environmental conditions, including exposure to Ca(2+) and Na(+), and induces gene expression by regulating the Crz1p/Tcn1p transcription factor. We used DNA microarrays to perform a comprehensive analysis of calcineurin/Crz1p-dependent gene expression following addition of Ca(2+) (200 mm) or Na(+) (0.8 m) to yeast. 163 genes exhibited increased expression that was reduced 50% or more by calcineurin inhibition. These calcineurin-dependent genes function in signaling pathways, ion/small molecule transport, cell wall maintenance, and vesicular transport, and include many open reading frames of previously unknown function. Three distinct gene classes were defined as follows: 28 genes displayed calcineurin-dependent induction in response to Ca(2+) and Na(+), 125 showed calcineurin-dependent expression following Ca(2+) but not Na(+) addition, and 10 were regulated by calcineurin in response to Na(+) but not Ca(2+). Analysis of crz1Delta cells established Crz1p as the major effector of calcineurin-regulated gene expression in yeast. We identified the Crz1p-binding site as 5'-GNGGC(G/T)CA-3' by in vitro site selection. A similar sequence, 5'-GAGGCTG-3', was identified as a common sequence motif in the upstream regions of calcineurin/ Crz1p-dependent genes. This finding is consistent with direct regulation of these genes by Crz1p.

Alternate JournalJ. Biol. Chem.